Brain Activation by Visual Food-Related Stimuli and Correlations with Metabolic and Hormonal Parameters: A fMRI Study

Regional brain activity in 15 healthy, normal weight males during processing of visual food stimuli in a satiated and a hungry state was examined and correlated with neuroendocrine factors known to be involved in hunger and satiated states. Two functional Magnetic Resonance Imaging (fMRI) sessions were performed with a one week interval, after overnight fasting or 1 hour after a standardized meal. Blood samples and appetite assessment were obtained after each fMRI session. Main effects of processing food versus non-food stimuli were observed in the ventral visual stream, including the fusiform gyrus and hippocampal areas bilaterally, significantly more in the fasting state. Leptin concentration correlated negatively with activity in the left hippocampal area and right insula during the satiation condition. A positive correlation between ghrelin and "thought of food" hunger scores were found. The positive correlation between ghrelin and food related activation in the insula areas and the right hippocampus during fasting did not reach significance. Conclusion: The increased activation of food vs non-food pictures in the ventral visual stream reflects increased salience of food pictures when subjects are hungry. Leptin was associated with activations in areas involved in processing of new information and emotion. © Jakobsdottir et al

Effects of growth hormone substitution therapy on cognitive functioning in growth hormone deficient patients: a functional MRI study

Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging. Copyright © 2006 S. Karger AG

The Interrelationship between Insulin-Like Growth Factor 1, Apolipoprotein E ε4, Lifestyle Factors, and the Aging Body and Brain

Aging is associated with a decrease in body and brain function and with a decline in insulin-like growth factor 1 levels. The observed associations between alterations in insulin-like growth factor 1 levels and cognitive functioning and Mild Cognitive Impairment suggest that altered insulin-like growth factor 1 signaling may accompany Alzheimer’s disease or is involved in the pathogenesis of the disease. Recent animal research has suggested a possible association between insulin-like growth factor 1 levels and the Apolipoprotein E ε4 allele, a genetic predisposition to Alzheimer’s disease. It is therefore hypothesized that a reduction in insulin-like growth factor 1 signaling may moderate the vulnerability to Alzheimer’s disease of human Apolipoprotein E ε4 carriers. We address the impact of age-related decline of insulin-like growth factor 1 levels on physical and brain function in healthy aging and Alzheimer’s disease and discuss the links between insulin-like growth factor 1 and the Apolipoprotein E ε4 polymorphism. Furthermore, we discuss lifestyle interventions that may increase insulin-like growth factor 1 serum levels, including physical activity and adherence to a protein rich diet and the possible benefits to the physical fitness and cognitive functioning of the aging population

Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults

Purpose: The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing’s disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). Methods: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. Results: At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. Conclusions: During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms

Age- and Sex-Related Interactions between Insulin-Like Growth Factor-I Promoter Polymorphisms and IGF-I Levels

The present study explored sex-and age-related interactions of IGF-I polymorphisms with IGF-I serum levels. In 2000 data on IGF-I promoter polymorphism and IGF-I level were available of 344 (mean age 36; 162 men) and 6 years later in 287 subjects (133 men). As the sample sizes of groups of subjects with IGF-I genotypes 192/192, 190/192, 192/194 and 192/196 were large enough to be analyzed, the relationship between these specific genotypes and IGF-I-level was determined. The results indicated that in women aged 36 IGF-I levels for genotype 190/192 (mean 29.24 nmol/l) were higher than those for genotypes 192/192 (mean 24.29), 192/194 (mean 24.61) and 192/196 (mean 23.93). Male IGFI levels were decreased in 2006 compared to 2000 for genotypes 192/192 (mean decline - 3.67), 192/194 (mean decline - 1.61), 192/196 (mean decline - 4.18), but not for 190/192. Female IGF-I levels were decreased for genotypes 192/192 (mean decline - 1.85) and 190/192 (mean decline - 4.64), but not for 192/194 and 192/196. Thus females with genotype 190/192 have higher IGF-I levels, while females with genotypes 192/194 or 192/196 and males with genotype 190/192 do not show a decline of IGF-I level. © van Turenhout et al

Synthetic smooth muscle cell phenotype is associated with increased nicotinamide adenine dinucleotide phosphate oxidase activity: Effect on collagen secretion

ObjectiveSmooth muscle cells (SMCs) from prosthetic vascular grafts secrete higher levels of collagen than aortic SMCs under basal conditions and during incubation with oxidized low-density lipoprotein. We postulated that reactive oxygen species (ROS) contributed to the observed difference. The objective of this study was to assess the effect of ROS on collagen secretion by aortic and graft SMCs and explore the mechanism involved.MethodsSMCs isolated from canine aorta or Dacron thoracoabdominal grafts were incubated with 6-anilinoquinoline-5,8-quinone (LY83583), an agent that induces superoxide production. Type I collagen in the conditioned medium was measured by enzyme-linked immunosorbent assay, and superoxide anion production was measured by lucigenin assay.ResultsLY83583 stimulated a rapid increase in collagen production by graft SMCs that paralleled the LY83583-induced increase in superoxide production. The increase in both collagen and superoxide was greater in graft SMCs than aortic SMCs. Collagen and superoxide production were inhibited by superoxide scavengers. Nicotinamide adenine dinucleotide phosphate (NADPH) induced significantly more superoxide production by graft SMCs than aortic SMCs, suggesting that the NADPH oxidase system was more active in graft SMCs. NADPH oxidase inhibitors blocked the superoxide and collagen production induced by LY83583.ConclusionIn SMCs, the synthetic phenotype is associated with increased NADPH oxidase activity and elevated superoxide production in response to an oxidative stress. Superoxide, in turn, leads to increased collagen production.Clinical RelevanceThe inflammatory process after prosthetic vascular graft implantation causes oxidative stress that can stimulate collagen production by graft SMCs, contributing to the progression of intimal hyperplasia. The exaggerated response of graft SMCs to oxidative stress offers a potential target for therapeutic interventions

Building, Reality, Caring: What Nurses in Three Australian Psychogeriatric Assessment Units Say about the Built Environment

Many people believe that ‘purpose-built’ facilities will diminish some of the challenging behaviours exhibited by older people with dementia or psychiatric conditions. This study aimed to explore and understand what hands-on nurses in psychogeriatric assessment units experience and think of the built environment as a part of their day to day work. Twenty-one unstructured interviews were conducted with nurses at three psychogeriatric assessment units. The units ranged in style from an ancient adapted building to a contemporary 'purpose-built' facility. A critical hermeneutics derived from Gadamer was used to explore the interviews. It found that nurses think of the built environment in relation to the care needs of their patients, and feel bureaucratic restrictions in using the built environment more keenly than the shortcomings of the built environment itself. Nurses saw themselves and their patients as 'outcasts' or victims of those with money and power. The study concludes with suggestions for challenging the status quo, but also considers that being regarded as 'outcasts' allows opportunities to avoid being overly impressed by technological marvels

Revisiting the role of insulin-like growth factor-I receptor stimulating activity and the apolipoprotein E in Alzheimer's disease

__Background:__ Alterations in insulin-like growth factor I (IGF-I) signaling have been associated with dementia and Alzheimer's disease (AD). Studies on the association between IGF-I levels and dementia risk have been inconclusive. We reported earlier that higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and incidence of dementia. __Objective:__ In the present study, we test the robustness of the association between IGF-I receptor stimulating activity and dementia by extending the follow-up period to 16 years and investigate possible effect modification by apolipoprotein E (ApoE). __Methods:__ At baseline, circulating IGF-I receptor stimulating activity was determined by the IGF-I kinase receptor activation (KIRA) assay in 1,014 elderly from the Rotterdam Study. Dementia was assessed from baseline (1997-1999) to follow-up in January 2015. Associations of IGF-I receptor stimulating activity and incident dementia were assessed with Cox proportional hazards models. __Results:__ During 10,752 person-years of follow-up, 174 people developed dementia. In the extended follow-up we no longer observed a dose-response relationship between IGF-I receptor stimulating activity and risk of dementia [adjusted odd